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Melanotan-2 Structure And Receptor Pharmacology — Reference Sheet

By Editorial Desk · published 2026-03-30 · last reviewed 2026-05-16 · Wiki

The short version of post-marketing surveillance fits in a sentence. The long version — which is the one that helps — is below.

This page was last updated on 2026-05-16 and is reviewed periodically as new material appears.

Melanotan-2 Structure and Receptor Pharmacology

Melanotan-2 is a synthetic cyclic heptapeptide designed as a structural analogue of alpha-melanocyte-stimulating hormone, the endogenous tridecapeptide that regulates pigment production. Two modifications distinguish it from the natural hormone: norleucine replaces methionine at the N-terminus, which limits oxidation, and a D-phenylalanine substitution raises receptor affinity. The ring is closed through an aspartate-lysine lactam bridge, giving the molecule a constrained conformation. The free base has a molecular mass near 1024 daltons, and commercial material is usually supplied as an acetate salt. It appears in the literature as a research peptide rather than an approved therapeutic agent.

Receptor studies place melanotan-2 among non-selective melanocortin agonists, binding MC1R, MC3R, MC4R and MC5R rather than a single subtype. Activation of MC1R on cutaneous melanocytes raises tyrosinase activity and shifts pigment synthesis toward eumelanin, which is darker and more photostable than pheomelanin. Central receptors, particularly MC4R, are associated with appetite suppression and with reported effects on sexual function. Because subtype selectivity is low, the same molecule engages pigment, metabolic and vascular pathways at once, and this breadth is a common explanation offered for the range of adverse events described in user reports.

No regulatory authority has approved melanotan-2 for human use, and several countries classify it as a prescription-only or controlled substance, which restricts lawful supply. Material sold online is generally labelled as a research chemical and is not required to meet pharmaceutical standards of identity or purity. Published human data consist mainly of small uncontrolled studies, case reports and adverse-event notifications, so the evidence base is descriptive rather than confirmatory. Whether repeated melanocyte stimulation alters long-term naevus behaviour remains an open question that no completed trial has resolved.

Handling, Storage, and Analytical Verification

Lyophilised melanotan-2 is supplied as a solid, which is more stable than a solution. The material is hygroscopic, so weighing is done quickly, in low humidity, with the container kept sealed. Reconstitution usually uses water for injection or bacteriostatic water, added down the wall of the vial to limit foaming. A reconstituted solution is held at 2 to 8 °C and kept away from light. Repeated freezing and thawing of the same vial is avoided because ice crystal formation and concentration effects degrade the peptide.

Reversed-phase high-performance liquid chromatography is the routine method for purity assessment. Peptides absorb near 214 nm because of the peptide bond, and a gradient of acetonitrile in water separates the intact peptide from deletion sequences, oxidised products, and earlier-eluting fragments at neutral pH. Electrospray ionisation mass spectrometry provides an orthogonal check: the measured mass must agree with the theoretical value. Amino acid analysis and peptide mapping confirm structure but are used less often. Reference standards remain scarce because the peptide is not described in any pharmacopoeia.

Melanotan-2 at a glance

PropertyValueNotes
Molecular formulaC50H69N15O9Free base; salt forms add to total mass
Molecular massAbout 1024 daltonsCalculated for the free base
Structural classCyclic heptapeptideContains D-phenylalanine and norleucine
Parent hormoneAlpha-melanocyte-stimulating hormoneEndogenous tridecapeptide of 13 residues
Receptor profileNon-selective melanocortin agonistInteracts with MC1R, MC3R, MC4R and MC5R

Chemical Background and Receptor Activity

Melanotan-2 is a synthetic cyclic heptapeptide designed as an analogue of alpha-melanocyte-stimulating hormone. Its sequence incorporates a lactam bridge that constrains the peptide into a ring, which increases resistance to enzymatic breakdown relative to the natural hormone. Researchers at the University of Arizona synthesised the compound in the late 1980s and early 1990s while studying pigmentation pathways. It has never received marketing approval from any national medicines regulator. In the scientific literature it is usually described as a laboratory research reagent rather than a therapeutic product.

The peptide acts as a non-selective agonist at melanocortin receptors, showing affinity for MC1R, MC3R, MC4R and MC5R. Activation of MC1R on melanocytes drives the conversion of tyrosine into melanin and shifts production toward the darker eumelanin form. MC4R signalling in the central nervous system is linked to appetite and energy balance, which helps explain why reduced food intake appeared in early human studies. Effects on MC4R and on vascular tone also account for the erectile responses recorded as unexpected findings in those same trials.

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Regulatory Status and Literature Discussion

Melanotan-2 has not received marketing authorisation from major regulatory agencies for any therapeutic indication. Several jurisdictions classify it as a prescription-only medicine or a controlled substance when supplied for human use. Because approved products do not exist, material sold online usually sits outside pharmaceutical supply chains and formal quality oversight. Regulators have issued public notices describing the compound as unapproved. Enforcement varies, and the legal position differs between countries, which complicates any single general statement about its status.

Scientific discussion of Melanotan-2 spans pharmacology, dermatology, and public-health literature. Laboratory studies examine its receptor binding and cellular effects, while clinical reports describe outcomes observed after unregulated use. These two bodies of work differ in rigour and intent. Peer-reviewed trials of the compound as a medicine are limited, so much of the available information comes from case reports and surveillance data. Authors frequently note the gap between experimental findings and real-world use.

Chemistry and Receptor Pharmacology

Melanotan II is a synthetic cyclic heptapeptide with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, corresponding to a molecular formula of C50H69N15O9 and a monoisotopic mass near 1024 daltons. It was designed as a structural analogue of alpha-melanocyte-stimulating hormone, a peptide hormone produced by cleavage of proopiomelanocortin. A lactam bridge between the aspartate and lysine side chains closes the ring, and the C-terminal amide removes a free carboxyl group. Both modifications increase resistance to enzymatic degradation compared with the linear parent hormone. Four substitutions distinguish it from afamelanotide, the linear analogue studied under the name melanotan I.

Receptor-binding studies classify melanotan II as a non-selective melanocortin agonist. It interacts with MC1R, MC3R, MC4R and MC5R, with reported affinities in the low nanomolar range and no strong subtype preference. Activation of MC1R on dermal melanocytes shifts pigment synthesis toward eumelanin, the dark polymer deposited in melanosomes and transferred to keratinocytes. Because the same peptide engages MC4R in the hypothalamus, it also appears in animal work on food intake and erectile response, which is why it is discussed in both pigment and metabolic research. Which receptor populations dominate after systemic exposure in humans is not fully established.

Further detail

A number of studies measuring anabolic steroid use in high school athletes found that out of all 12th grade students, 6.6 percent of them had used anabolic steroids at some point in their high school careers or were approached and counseled to use them. Of those students who acknowledged doping with anabolic–androgenic steroids, well over half participated in school-sponsored athletics, including football, wrestling, track and field, and baseball. A second study showed 6.3 percent of high school student Football players admitted to current or former AAS use. At the collegiate level, surveys show that AAS use among athletes range from 5 percent to 20 percent and continues to rise. The study found that skin changes were an early marker of steroid use in young athletes, and underscored the important role that dermatologists could play in the early detection and intervention in these athletes.

=== Amino acids === Of the Free Amino Nitrogen (FAN) that make up YAN, the amino acids arginine, proline and glutamine are the most abundant followed by alanine, threonine, serine and aspartic acid in much smaller concentrations though trace amounts of most known amino acids can be found in grape must. Proline is usually the most concentrated and can represent up to 30% of the total amount of amino acids. The exact amount FAN will vary and can range 22 to 1242 mg of nitrogen/liter of YAN being derived from free amino acids.

== Definition == An element of a flowing liquid or gas will endure forces from the surrounding fluid, including viscous stress forces that cause it to gradually deform over time. These forces can be mathematically first order approximated by a viscous stress tensor, usually denoted by

Sources: en.wikipedia.org

Supporting material

==== The Mariam Appeal ==== In 1998, Galloway founded the Mariam Appeal which was intended, according to its website's welcome page in 1999, "to campaign against sanctions on Iraq which are having disastrous effects on the ordinary people of Iraq". The campaign was named after Mariam Hamza, a child flown by the fund from Iraq to Britain to receive treatment for leukaemia. The intention was to raise awareness of the suffering and death of hundreds of thousands of other Iraqi children, due to poor health conditions and lack of suitable medicines and facilities, and to campaign for the lifting of the Iraq sanctions that many maintained were responsible for that situation. In 1999, Galloway was criticised for spending Christmas in Iraq with Tariq Aziz, who was Iraq's Deputy Prime Minister. In a 17 May 2005 hearing of the United States Senate Committee on Homeland Security and Governmental Affairs Permanent Subcommittee on Investigations, Galloway stated that he had many meetings with Aziz, and characterised their relationship as friendly. He said at another occasion that he and Aziz met more than ten times. During the 2003 invasion of Iraq, the fund received scrutiny after a complaint that Galloway used some donated money to pay for his travel expenses. He responded by stating that the expenses were incurred in his capacity as the appeal's chairman. Although the Mariam Appeal was never a registered charity and never intended to be such, it was investigated by the Charity Commission.

Hydroxymethylfurfural (HMF), also known as 5-(hydroxymethyl)furfural, is an organic compound formed by the dehydration of reducing sugars. It is a white low-melting solid (although commercial samples are often yellow) which is highly soluble in both water and organic solvents. The molecule consists of a furan ring, containing both aldehyde and alcohol functional groups. HMF can form in sugar-containing food, particularly as a result of heating or cooking. Its formation has been the topic of significant study as HMF was regarded as being potentially carcinogenic to humans. However, so far in vivo genotoxicity was negative. No relevance for humans concerning carcinogenic and genotoxic effects can be derived. HMF is classified as a food improvement agent and is primarily being used in the food industry in form of a food additive as a biomarker as well as a flavoring agent for food products. It is also produced industrially on a modest scale as a carbon-neutral feedstock for the production of fuels and other chemicals.

alpha helix (α-helix) A common structural motif in the secondary structures of proteins consisting of a right-handed helix conformation resulting from hydrogen bonding between amino acid residues which are not immediately adjacent to each other.

Sources: en.wikipedia.org

Supporting material

=== Hypothalamus === In turn, the hypothalamus controls the release of hormones from the anterior pituitary by secreting a class of hypothalamic neurohormones called releasing and release-inhibiting hormones—which are released to the hypothalamo-hypophyseal portal system and act on the anterior pituitary.

Drug-related violence remained at previous levels during the first months of López Obrador's presidency. In October 2019, a National Guard operation in Culiacán, Sinaloa to capture Ovidio Guzmán López, responding to a U.S. extradition request, failed after cartel gunmen took hostages and forced his release. Guzmán was released after approximately 700 cartel enforcers took multiple hostages, including the housing unit where military families live in Culiacán. López Obrador defended the decision to release Guzmán López, arguing it prevented further loss of life, and insisted that he wanted to avoid more massacres, and that even though they underestimated the cartel's forces and ability to respond, the criminal process against Ovidio is still ongoing. Guzmán López was captured in a 2023 operation and extradited to the U.S. The strategy of avoiding armed confrontations while drug organizations have continued violent altercations has been controversial. The Jalisco New Generation Cartel (CJNG) expanded aggressively during López Obrador's presidency, and its territorial disputes were linked to significant increases in homicide rates in Colima, Zacatecas, Guanajuato, and Jalisco. In July 2022, authorities captured Rafael Caro-Quintero, a former leader of the Guadalajara Cartel. Despite his campaign promises, military deployments and expenditures have risen, with troop levels 76% higher and defense spending up 87% between 2012 and 2022.

== Career == Strobel earned a bachelor's degree in biochemistry from Brigham Young University and a Ph.D. in biology from the California Institute of Technology, under the guidance of Peter Dervan, before doing postdoctoral research at the University of Colorado, Boulder, under the mentorship of Thomas Cech. He has been a professor with the Howard Hughes Medical Institute (HHMI) since 2006. He joined the Yale faculty in 1995 in the Department of Molecular Biophysics & Biochemistry and served as department chair from 2006 to 2009. Since 2011, he has served as vice president for West Campus Planning & Program Development, where he has directed the expansion of the West Campus as a research and educational center. In 2014, he also became the inaugural deputy provost for Teaching & Learning. In this capacity, he has overseen the creation of the Yale Poorvu Center for Teaching and Learning, housed within the Sterling Memorial Library. The center provides teaching resources and support to Yale faculty, postdocs, graduate students and undergraduate students.

Sources: en.wikipedia.org

Frequently asked questions

Is melanotan-2 approved for medical use?

No regulatory agency has authorised melanotan-2 as a medicine for any indication. It circulates mainly as a research chemical or through unregulated channels. As a result, identity, purity and content are not independently guaranteed.

How does melanotan-2 differ from melanotan-1?

Melanotan-1, also called afamelanotide, is a linear analogue with greater selectivity for MC1R and has received approval in some jurisdictions for a specific photosensitivity disorder. Melanotan-2 is cyclic, less selective, and reaches central receptors more readily. The two are often confused in online discussion despite different pharmacology and regulatory status.

What is the connection to alpha-MSH?

Alpha-MSH is an endogenous tridecapeptide derived from pro-opiomelanocortin. Melanotan-2 reproduces its core receptor-binding sequence inside a shortened, stabilised ring. The result is a molecule with a longer effective half-life and higher potency than the parent hormone.

Why are freeze-dried peptides kept cold?

Low temperature slows hydrolysis and oxidation, the two main routes by which the peptide backbone and side chains are modified. A lyophilised powder stored at −20 °C is more stable than one kept at room temperature, and once the material is dissolved the degradation rate rises, making refrigeration more important.

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